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The first record of the outbreak in Hong Kong appeared on 13 July 1968. By the end of July 1968, extensive outbreaks were reported in Vietnam and Singapore. Despite the fatality of the 1957 Asian Flu in China, little improvement had been made regarding the handling of such epidemics. The Times newspaper was actually the first source to sound alarm regarding this new possible pandemic.

By September 1968, the flu reached India, the Philippines, northern Australia and Europe. That same month, the virus entered California from returning Vietnam Wartroops but did not become widespread in the United States until December 1968. It would reach Japan, Africa and South America by 1969.[4] The outbreak in Hong Kong, where density is about 500 people per acre, reached maximum intensity in two weeks, lasting six months in total from July to December 1968, however worldwide deaths from this virus peaked much later, in December 1968 and January 1969. By that time, public health warnings[5] and virus descriptions[6] were issued in the scientific and medical journals.

The influenzaviruses that caused the Hong Kong flu. (magnified approximately 100,000 times)

The Hong Kong flu was the first known outbreak of the H3N2 strain, though there is serologic evidence of H3N1 infections in the late 19th century. The virus was isolated in Queen Mary Hospital.

In the 1968 pandemic vaccine became available one month after the outbreaks peaked in the US.

Both the H2N2 and H3N2 pandemic flu strains contained genes from avian influenza viruses. The new subtypes arose in pigs coinfected with avian and human viruses and were soon transferred to humans. Swine were considered the original "intermediate host" for influenza, because they supported reassortment of divergent subtypes. However, other hosts appear capable of similar coinfection (e.g., many poultry species), and direct transmission of avian viruses to humans is possible. H1N1 may have been transmitted directly from birds to humans (Belshe 2005).[9]

The Hong Kong flu strain shared internal genes and the neuraminidase with the 1957 Asian Flu (H2N2). Accumulated antibodies to the neuraminidase or internal proteins may have resulted in much fewer casualties than most pandemics. However, cross-immunity within and between subtypes of influenza is poorly understood.

"Three strains of Hong Kong influenza virus isolated from humans were compared with a strain isolated from a calf for their ability to cause disease in calves. One of the human strains. A/Aichi/2/68, was detected for five days in a calf, but all three failed to cause signs of disease. Strain A/cal/Duschanbe/55/71 could be detected for seven days and caused an influenza-like illness in calves."[10]